Short-term effects of graded levels of theobromine in laboratory rodents

Abstract

Theobromine was added to the diet of mature and immature male and female rats in concentrations of 0.0, 0.2, 0.4, 0.6, 0.8, or 1.0% in diets containing 22 or 10% casein and these diets were fed for 28 days. The prominent effects of increasing concentrations of dietary theobromine were anorexia (except in female rats given the 22% casein diet), decreases in body weight in mature rats, growth retardation in immature rats and atrophy of the thymus glands in rats of both sexes and testicular atrophy in male rats. Atrophy of the thymus gland and of the testes became prominent at the 0.6% die any theobromine level. There was a progressive decrease in thymic cortical lymphocytes with increasing intake of theobromine, and at the 1% level the shrunken thymus gland was composed only of stromal cells and scattered medullary lymphocytes. Testicular changes included seminiferous tubular cell degeneration and necrosis and multinucleate cell formation with degeneration and necrosis at the higher theobromine levels. A low protein diet enhanced the severity of theobromine effects on body weight and growth and on thymic and testicular weight changes and histopathology. The daily dose of theobromine which produced retrogressive changes in weight patterns and in the morphology of the thymus in both sexes and of the testes in males was approximately 250–300 mg/kg/day in mature rats and approximately 500 mg/kg/day in immature rats. Hamsters and mice were much more resistant to theobromine than were rats. A decrease in growth and in thymic weights occurred only at the highest dose levels of theobromine and testicular and thymic changes were completely absent in hamsters. Testicular changes in mice were seen only at dietary theobromine concentrations which produced considerable mortality.